Apparatus and method for controlling ablation depth

ABSTRACT

During an ablation procedure in a chamber of the heart RF energy is used to form a myocardial lesion for treatment of some arrhythmias such as sustained supraventricular tachycardia and accessory pathways. A galvanic cell, formed by a metallic electrode having a first work function at the ablation site, a second metallic electrode having a second work function located remote from the ablation site and the intervening tissue serving as an electrolyte, produces an output current signal reflective of the formation of a lesion at the ablation site and is used to control the RF energy applied. A curve depicting the output current signal has a maximum value at the point a burn or lesion begins and thereafter begins to decrease in value. A short duration inflection or bump of the curve occurs prior to charring and carbonization of the lesion and predicts lesion formation of a sufficient depth. Thereafter, RF energy should no longer be applied to prevent unnecessary damage to the myocardial tissue. The bump in the curve serves as an accurate indicator to a physician of successful formation of the lesion.

CROSS-REFERENCE TO RELATED APPLICATION

The present application is based upon a disclosure contained inprovisional application entitled "APPARATUS AND METHOD FOR CONTROLLINGABLATION DEPTH" assigned Ser. No. 60/067,255, filed Dec. 2, 1997 and isa continuation-in-part of an application entitled "APPARATUS AND METHODFOR DETERMINING ABLATION", assigned Ser. No. 08/851,879, filed May 6,1997, now U.S. Pat. No. 5,868,737, which includes subject matterdisclosed in provisional application entitled "APPARATUS AND METHOD FORINDICATING THERMAL ABLATION" assigned Ser. No. 60/016,647, filed May 15,1996 and is a continuation-in-part of an application entitled "APPARATUSAND METHOD FOR THERMAL ABLATION" assigned Ser. No. 08/488,887, filedJun. 9, 1995, now U.S. Pat. No. 5,697,925, all of which applications areassigned to the present assignee.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates to apparatus for ablating tissue and, moreparticularly, to an unambiguous formation of a lesion at an ablationsite.

2. Background of the Invention

The heart is a four chamber muscular organ (myocardium) that pumps bloodthrough various conduits to and from all parts of the body. In orderthat the blood be moved in the cardiovascular system in an orderlymanner, it is necessary that the heart muscles contract and relax in anorderly sequence and that the valves of the system open and close atproper times during the cycle. Specialized conduction pathways conveyelectrical impulses swiftly to the entire cardiac muscle. In response tothe impulses, the muscle contracts first at the top of the heart andfollows thereafter to the bottom of the heart. As contraction begins,oxygen depleted venous blood is squeezed out of the right atrium (one oftwo small upper chambers) and into the larger right ventricle below. Theright ventricle ejects the blood into the pulmonary circulation, whichresupplies oxygen and delivers the blood to the left side of the heart.In parallel with the events on the right side, the heart muscle pumpsnewly oxygenated blood from the left atrium into the left ventricle andfrom there out to the aorta which distributes the blood to every part ofthe body. The signals giving rise to these machinations emanates from acluster of conduction tissue cells collectively known as the sinoatrial(SA) node. The sinoatrial node, located at the top of the atrium,establishes the tempo of the heartbeat. Hence, it is often referred toas the cardiac pacemaker. It sets the tempo simply because it issuesimpulses more frequently than do other cardiac regions. Although thesinoatrial node can respond to signals from outside the heart, itusually becomes active spontaneously. From the sinoatrial node impulsesrace to the atrioventricular (AV) node above the ventricles and speedsalong the septum to the bottom of the heart and up along its sides. Theimpulses also migrate from conduction fibers across the overlying musclefrom the endocardium to the epicardium to trigger contractions thatforce blood through the heart and into the arterial circulation. Thespread of electricity through a healthy heart gives rise to the familiarelectrocardiogram. Defective or diseased cells are electricallyabnormal. That is, they may conduct impulses unusually slowly or firewhen they would typically be silent. These diseased cells or areas mightperturb smooth signaling by forming a reentrant circuit in the muscle.Such a circuit is a pathway of electrical conduction through whichimpulses can cycle repeatedly without dying out. The resulting impulsescan provoke sustained ventricular tachycardia: excessively rapid pumpingby the ventricles. Tachycardia dysrhythmia may impose substantial riskto a patient because a diseased heart cannot usually tolerate rapidrates for extensive periods. Such rapid rates may cause hypotension andheart failure. Where there is an underlying cardiac disease, tachycardiacan degenerate into a more serious ventricular dysrhythmia, such asfibrillation. By eliminating a reentrant circuit or signal pathwaycontributing to tachycardia, the source of errant electrical impulseswill be eliminated. Ablation of the site attendant such a pathway willeliminate the source of errant impulses and the resulting arrhythmia.Mapping techniques for locating each of such sites that may be presentare well known and are presently used.

Interruption of the errant electrical impulses is generally achieved byablating the appropriate site. Such ablation has been performed bylasers. The most common technique used at an ablation site involves theuse of a probe energized by radio frequency radiation (RF). Measurementand control of the applied RF energy is through a thermistor (or itcould be a thermocouple) located proximate the RF element at the tip ofa catheter probe. While such a thermistor may be sufficiently accurateto reflect the temperature of the thermistor, it is inherentlyinaccurate in determining the temperature of the tissue at the ablationsite. This results from several causes. First, there is a temperatureloss across the interface between the ablation site (usually variabledue to position of electrode) and the surface of the RF tip. Second, theflow of blood about the non-tissue contact portion of the conductive RFtip draws off heat from the ablation site which causes the thermistor tobe cooler than the tissue under ablation. However, temperatures above100° C. causes coagulum formation on the RF tip, a rapid rise inelectrical impedance of the RF tip, and excessive damage to theendocardium. Third, there is a lag in thermal conduction between the RFtip and the thermistor, which lag is a function of materials, distance,and temperature differential. Each of these variables may changeconstantly during an ablation procedure.

To ensure that the ablation site tissue is subjected to heat sufficientto raise its temperature to perform irreversible tissue damage, thepower transmitted to the RF tip must be increased significantly greaterthan that desired for the ablation in view of the variable losses. Dueto the errors of the catheter/thermistor temperature sensing systems,there is a propensity to overheat the ablation site tissue needlessly.This creates three potentially injurious conditions. First, the RF tipmay become coagulated. Second, tissue at the ablation site may "stickto" the RF tip and result in tearing of the tissue upon removal of theprobe. This condition is particularly dangerous when the ablation siteis on a thin wall of tissue. Third, inadequate tissue temperaturecontrol can result in unnecessary injury to the heart includingimmediate or subsequent perforation.

When radio frequency current is conducted through tissue, as might occurduring a procedure of ablating a tissue site on the interior wall(endocardium) of the heart with a radio frequency energized catheter,heating occurs preliminarily at the myocardial tissue interface with thetip of the catheter. Given a fixed power level and geometry of thecatheter probe, the temperature gradient from the probe interface and adistance, r, into the tissue is proportional to 1/r⁴. Heating is causedby the resistive (OHMIC) property of the myocardial tissue and it isdirectly proportional to the current density. As may be expected, thehighest temperature occurs at the ablation site which is at theinterface of the RF tip and the tissue.

When the temperature of the tissue at the ablation site approaches 100°C., a deposit is formed on the RF tip that will restrict the electricalconducting surface of the RF tip. The input impedance to the RF tip willincrease. Were the power level maintained constant, the interfacecurrent density would increase and eventually carbonization would occur.At these relatively extreme temperatures, the RF tip will often stick tothe surface of the tissue and may tear the tissue when the RF tip isremoved from the ablation site.

To effect ablation, or render the tissue nonviable, the tissuetemperature must exceed 50° C. If the parameters of the RF tip of acatheter are held constant, the size and depth of the lesion caused bythe ablation is directly proportional to the temperature and time at theinterface (assuming a time constant sufficient for thermal equilibrium).In order to produce lesions of greatest depth without overheating thetissues at the interface, critical temperature measurement techniques ofthe RF tip are required.

The current technology for measuring the temperature of an RF tipembodies a miniature thermistor(s) located in the RF tip of the probe.The present state of the art provides inadequate compensation for thethermal resistance that exists between the thermistor and the outersurface of the RF tip, which may be in variable contact with the tissueand affected by blood cooling or between the outer surface of the RF tipand the surface of the adjacent tissue. Because of these uncertaintiescontributing to a determination of the specific temperature of thetissue at the interface, apparatus for accurately determining whenablation actually occurs would be of great advantage in performing anelectrophysiological procedure to ablate a specific site(s) of themyocardial tissue.

SUMMARY OF THE INVENTION

A catheter probe having a metal tip energized by an RF generatorradiates RF energy as a function of the RF energy applied. When the tipor a first metallic electrode located proximally from the tip of theprobe is placed adjacent tissue at an ablation site, the irradiating RFenergy heats the tissue due to the ohmically resistive property of thetissue. The first electrode having a first work function placed adjacentthe ablation site on tissue in combination with an electricallyconducting dissimilar metallic second electrode independent of or partof the probe having a second work function in contact with tissue at alocation remote from the ablation site and an electrolyte defined by theintervening tissue create a galvanic cell because of migration ofelectrical charges therebetween. By loading the galvanic cell, the DCoutput current signal is a linear function of the temperature of theablation site heated by the RF energy. The DC output current signal ofthe galvanic cell is used to regulate the output of the RF generatorapplied to the first electrode to control the current density at theablation site. When ablation at the ablation site begins to occur, thevalue of the DC output current signal drops dramatically irrespective offurther applied RF energy. Prior to carbonization at the ablation site,coagulation of the first electrode, sticking of the tissue to the firstelectrode and possible perforation of the tissue, the value of the DCoutput current signal exhibits an inflection or bump before continuingto decrease. This bump serves as an indicator to terminate furtherapplication of RF energy as a lesion of sufficient size and depth willhave been formed.

It is therefore a primary object of the present invention to provide asignal for indicating the process of myocardial lesion formation.

Another object of the present invention is to provide an output signalrepresentative of the occurrence of tissue damage at an ablation sitefor terminating further RF radiation of the ablation site.

Yet another object of the present invention is to generate a signalrepresentative of actual tissue damage at an ablation site in order tocease further heating of the ablation site by regulating the radiationof RF energy from an ablating RF electrode.

Still another object of the present invention is to provide apparatusfor determining the occurrence of tissue damage of a cardiac impulsepathway and thereafter cease further heating of the ablation site.

A further object of the present invention is to provide aself-regulating catheter mounted RF radiating element controlled by anoutput signal reflective of actual tissue damage at an ablation site onthe endocardium of a heart suffering tachycardia dysrhythmia and destroya pathway of errant electrical impulses at least partly contributing tothe tachycardia dysrhythmia.

A still further object of the present invention is to provide a methodfor controlling heating and sensing the occurrence of desired depth oftissue damage at an ablation site and thereafter terminating furtherablation of the ablation site.

These and other objects of the present invention will become apparent tothose skilled in the art as the description thereof proceeds.

BRIEF DESCRIPTION OF THE DRAWINGS

The present invention may be described with greater specificity andclarity with reference to the following drawings, in which:

FIG. 1 illustrates a simplified representation of the present invention;

FIG. 2 illustrates the current density at an ablation site during anablation procedure;

FIG. 3 illustrates a representation of a catheter probe embodying athermistor useful in the present invention;

FIG. 4 illustrates representatives curves for calibrating thetemperature of an ablation site through use of a probe embodying athermistor;

FIG. 5 is a block diagram of circuitry representatively shown in FIG. 1;

FIG. 6 illustrates a catheter probe for sequentially mapping theendocardium, identifying a site to be ablated and ablating the sitewithout relocating the probe;

FIGS. 7A and 7B are graphs illustrating the respective output signals ofthe power level applied by a catheter tip, the temperature sensed by acatheter mounted thermistor and the galvanic current at an ablation siteduring an ablation procedure;

FIG. 8 illustrates the use of a computer to perform certain of thefunctions manually performed with the circuitry shown in FIG. 5 and toprovide displays of information;

FIG. 9 illustrates the components for conducting in vitro tests todetermine the amplitude per time of the curve depicting the outputcurrent signal of the galvanic cell (bio-battery) during an ablationprocedure, other signals, including impedance, power and temperature arealso derivable;

FIG. 10 illustrates a representative recording during an in vitroexperiment of the bio-battery signal (in m V), the electrode tissuetemperature (in ° C.), the tissue impedance (in Ω) and the RF energy (involts);

FIG. 11 illustrates a typical bio-battery output current signalgenerated during in vitro and in vivo experiments;

FIG. 12 illustrates relative depths of the lesions formed at differentpower turn off points on the bio-battery output current signal shown inFIG. 11; and

FIG. 13 illustrates representative curves for the bio-battery outputcurrent signal, temperature, impedance and RF power level during an invivo experiment.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

Two electrodes of different metals having different work functions inthe presence of an electrolyte (such as blood) a saline solution orliving tissue, will produce an exchange of electrical charges and anelectromotive force (emf) is generated. This emf generator is known as agalvanic cell. A technical discussion of the history of galvanic cellsis set forth in Chapter 1.3, entitled "Basic Electrochemistry" (pages12-31) in a textbook entitled Modern Electrochemistry, authored by JohnO'M. Bockris, published by Plenum Press., New York, dated 1970. Detailedtechnical discussions of galvanic cells can be found in: Chapter 4,entitled "Reversible Electrode Potentials" (pages 73-100) of a textbookentitled Electrochemistry Principles and Applications, authored byEdmund C. Potter, published by Cleaver-Hume Press, Ltd., dated 1956;Chapter 4 entitled "Electrodes and Electrochemical Cells" (pages 59-89)of a textbook entitled Introduction to Electrochemistry, authored by D.Bryan Hibbert, published by MacMillan Press Ltd., dated 1993; andChapter 12 entitled "Reversible Cells" (pages 282-311) of a textbookentitled Electrochemistry of Solutions, authored by S. Glasstone,published by Methuen & Co. Ltd., London, dated 1937 (Second Edition).These technical discussions are incorporated herein by reference.

The magnitude of the potential of a galvanic cell is a function of theelectrolyte concentrates and the metals' work functions. The opencircuit voltage of the galvanic cell is essentially constant despitetemperature changes at the interface between the electrodes and theelectrolyte. However, by loading the galvanic cell with a fixed valueshunt resistance it simulates a current generator which has an outputsignal directly proportional to the temperature of the metal andelectrolyte interface. The output signal of the current generator can becalibrated as a function of the temperature at the interface. A simplemethod for calibration is that of referencing the output of the currentgenerator with the output of a thermistor embedded in the electrode atsteady state power and temperature conditions at an initial or firsttemperature and at a second temperature. This will provide two datapoints for the power/temperature curve of the current generator. Sincethe output of the current generator is linear, the curve can be extendedto include all temperatures of interest.

The present invention is directed to apparatus for ablating an errantcardiac conduction pathway responsible for or contributing to arrhythmiaof the heart. The ablation process is performed by heating the ablationsite tissue to a temperature typically exceeding 50° C., sufficient tocause ablation of the cells contributing to the errant impulse pathway.The ablation is effected by irradiating the ablation site tissue withradio frequency (RF) energy. For this purpose, a catheter probe tip ispositioned adjacent the ablation site, which site has been previouslydetermined by mapping procedures well known to physicians and thoseskilled in the art. Upon positioning of the probe tip or other electrodeof a probe at the ablation site, a source of RF energy is actuated totransmit RF energy through a conductor to the tip of the probe. The RFenergy radiates from the tip into the ablation site tissue. The currentdensity at the ablation site is a function of the power of the RF energyirradiating the ablation site and the surface area defining theinterface between the tip and the ablation site tissue. Control of thetissue temperature at the interface is of significant importance tocontrol the area and depth of ablation in order to perform the degree ofablation necessary, to prevent coagulation on the tip, to prevent thetip from sticking to the tissue, to prevent avoidable injury to adjacenttissue, to prevent perforation of the tissue, and to avoid unnecessaryheating of the blood flowing in and about the tip.

Catheter probes having a thermistor embedded at the tip have been usedto perform an ablation procedure and the amount of RF energy applied hasbeen regulated as a function of the temperature sensed by thethermistor. Such temperature sensing is inherently inaccurate indetermining the temperature at the ablation site due to the numerousvariables present. First, there exists a temperature loss through theinterface between the ablation site and the surface area of the tip incontact with tissue. Second, there exists a thermal resistance withinthe tip which causes temperature lag between the surface area of the tipin contact with the ablation site and the thermistor. Third, theorientation of the tip with respect to the ablation site will vary witha consequent variation of heating of the ablation site. Finally, theblood flowing about the tip area not in tissue contact will draw offheat as a function of both flow rate and orientation of the tip withrespect thereto. By experiment, it has been learned that the differencesbetween the tissue temperature at the ablation site and the temperatureregistered by a thermistor may range from 10° C. to 35° C. Suchtemperature excursion may result in unnecessary injury without aphysician being aware of the injury caused at the time of the ablationprocedure. Where ablation is being performed upon a thin wallmyocardium, a puncture or a perforation at a later time can and doesoccur with potentially disastrous results.

The present invention is shown in simplified format in FIG. 1. An RFgenerator 10 serves as a source of RF energy. The output of the RFgenerator is controlled by an input signal identified as J₁. The RFenergy, as controlled by J₁, is transmitted through a conductor 12 to acatheter probe 14. This probe is depicted as being lodged within a bloodfilled chamber 16 of a heart. The chamber may be the right or leftatrium or the right or left ventricle. Probe 14 is lodged adjacent, forinstance, tissue 18 at an ablation site 20 representing a reentrantcircuit to be ablated. As represented, blood continually flows throughchamber 16 about and around probe 14.

Probe 14 includes a tip 30 electrically connected to conductor 12 toirradiate ablation site 20 with RF energy. Typically, the frequency maybe in the range of about 350 kHz to about 1200 kHz. Such irradiation ofthe ablation site will result in heating of the ablation site as afunction of the current density at the ablation site. The currentdensity is determined by the energy level of the irradiating RF energyand the surface area of the ablation site. More specifically, the heatgenerated is proportional to the current density squared. This may beexpressed as: T(r)=kPd=kI² R=(J_(o) ² /r⁴) R, where T=temperature,r=distance from the interface, J_(o) =current density at the interface,Pd=power dissipated, I=current at the interface, and R=resistance at theinterface. The return path to RF generator 10 is represented byconductor 32. Conductor 32 is electrically connected to a relativelylarge sized plate 34 placed adjacent the patient's skin, preferably alarge surface area of the patient's back. To ensure good electricalcontact, an electrically conducting salve may be disposed intermediateplate 34 and patient's back 36. The fluid and tissues of the patientintermediate tip 30 and plate 34, represented by numeral 38,constitutes, in combination, an electrolyte and therefore anelectrically conductive path between the tip and the plate. The DCcurrent flow is represented by i_(s) and the DC voltage is representedby v_(s).

As more particularly illustrated in FIG. 2, ablation site has arelatively high concentration of current paths, representativelydepicted by diverging lines identified with numerals 42, 44, 46, 48, 50,and 52. These current paths are in close proximity with one another atthe ablation site. The resulting high current density will produceheating of the ablation site as a function of the current density. Thedepth of the ablated tissue is representatively illustrated by line 54.The current density proximate back 36 of the patient adjacent plate 34is relatively low. With such low current density, essentially no heatingof the skin adjacent plate 34 will occur. It is to be appreciated thatFIG. 2 is not drawn to scale and is intended to be solely representativeof relative current densities resulting from irradiation of an ablationsite by tip 30.

Ablation with tissue temperature control permits the physician tooptimize the ablation process by allowing the ablation to occur atmaximum temperature that is below a temperature conducive to formationof coagulation on the tip. Since such temperature is a function of theRF energy irradiating the ablation site tissue, control of the amount ofRF energy transmitted via conductor 12 to the tip is necessary. Apresently available type of catheter probe 60 is illustrated in FIG. 3.This probe includes a tip 62 for radiating RF energy received throughconductor 64 from a source of RF energy. A thermistor 66 is embedded intip 62 or in sufficient proximity with the tip to be responsive to thetemperature of the tip. A pair of conductors 68 and 70 interconnectthermistor 66 with a signal detection circuit to provide an outputsignal representative of the temperature sensed. Furthermore, probe 60may include mapping electrodes 72, 74 and 76. These electrodes may beused in conjunction with manipulation of probe 60 within the heart todetect and identify errant impulse pathways causing cardiac arrhythmia.Conductors 78, 80 and 82 connect electrodes 72, 74 and 76, respectively,to circuitry associated with the mapping functions, as is well known.

As stated above, thermistor 66 is incapable of providing an accuraterepresentation of the temperature at the ablation site. In summary, thecauses contributing to inaccurate temperature representation are heatloss through the interface between tip 30 and ablation site 20 (see FIG.2), thermal lag between the area of tissue in contact with the tip andthe sensing element of the thermistor, and heat loss resulting from flowof blood about the tip area not in contact with the tissue.

By experimentation, it has been learned that the combination of tip 30,plate 34 and body 38 perform in the manner of a galvanic cell providedthat the tip and the plate are metallic and of different work functionssince body 38 acts as an electrolyte; the body is permeated by fluidshaving electrical properties similar to a saline solution. Experimentsindicate that a preferable material for tip 30 is platinum and apreferable material for plate 34 is copper. The open circuit voltage(v_(s)) of this galvanic cell is essentially independent of thetemperature of ablation site 20. However, if the galvanic cell isheavily loaded with a shunt resistor, the galvanic cell serves as acurrent source and the magnitude of the current (i_(s)) is linear as afunction of the tissue temperature at the ablation site through the 37°C. to 100° C. temperature range of interest. The temperature of thetissue adjacent plate 34 is the body temperature since the currentdensity is insufficient to generate heat of any consequence. Thus, thegalvanic cell created by the apparatus illustrated in FIG. 2 provides anoutput signal representative of the tissue temperature at ablation site20 and irrespective of the temperature of tip 30.

One method for calibrating the galvanic cell will be described, butother methods may be used which do not require the presence of athermistor at the tip. A thermistor is embedded in the tip of a catheterprobe, such as probe 60. For reasons set forth above, the output of thethermistor is inherently inaccurate with respect to the actual tissuetemperature at the ablation site; moreover, the temperature sensed bythe thermistor as a function of the power applied is generallynonlinear. However, within a temperature range from a quiescent standbystate to a small temperature increase at the ablation site (smallincrease in power applied), the output signal of the thermistor isessentially linear. By matching the output curve of the thermistor withthe generally linear response curve of the galvanic cell, two coincidentreference points can be determined. Referring to FIG. 4, there isillustrated a thermistor response curve and a galvanic cell responsecurve manipulated to be coincident from a point 0 to a point 1. Bycorrelating the temperature indication of the thermistor at these twopoints, with the current output (i_(s)) of the galvanic cell, thetemperature response can be linearly extrapolated to obtain atemperature reading correlated with the current output of the galvaniccell. That is, for any given current output of the galvanic cell, thetissue temperature of the ablation site can be determined. Thus, ifprobe 14 illustrated in FIGS. 1 and 2 is of the type shown in FIG. 3,calibration of the probe at the ablation site can be readily determined.Other methods for calibrating the current output with temperature canalso be employed, as set forth above.

Referring to FIG. 5, there is illustrated a block diagram of the majorcomponents necessary to control the power applied to a catheter probefor ablating an errant impulse pathway at an ablation site. FIG. 5 showsa temperature input circuit 90 for setting a reference voltageequivalent to the tissue temperature sought for an ablation site atwhich an ablation procedure is to be performed. The resulting outputsignal is transmitted through conductor 92 to a servo amplifier 94. Theservo amplifier provides an output signal on conductor 96 to control theoutput power of RF generator 98. A switch 100 controls operation of theRF generator. The RF energy output is impressed upon conductor 102. Ablocking capacitor 104 is representative of a high pass filter andblocks any DC component of the signal on conductor 102. Conductor 106interconnects the blocking capacitor with tip 30 of probe 14 andtransmits RF energy to the tip. Tip 30 irradiates ablation site 20 of anendocardium, wall, membrane, or other living tissue to be irradiatedwith RF energy. Tip 30 is of a substance, such as platinum or othermetal, having a first work function. Plate 34 displaced from tip 30, isof a substance, such as copper or other metal, having a second workfunction which is different from the first work function. Plate 34 is inelectrical contact with a mass of tissue 38 intermediate tip 30 and theplate. This tissue, being essentially a liquid and having electricalcharacteristics of a saline solution, serves in the manner of anelectrolyte interconnecting tip 30 and plate 34. The resulting galvaniccell formed, as discussed above, provides a DC output voltage v_(s)across conductors 106 and 108. Shunt impedance R1 heavily loads thegalvanic cell formed to convert the galvanic cell to a current source(i_(s)) to provide an output signal reflective of the tissue temperatureat ablation site 20. The output signal from the galvanic cell istransmitted through conductor 110 to a lowpass filter 112. The output ofthe lowpass filter is conveyed via conductor 114 to an operationalamplifier 120 of a calibration circuit 116. Additionally, a signalmeasurement and processing circuit 118, connected to conductor 102through conductor 103 to provide sampling of the output load voltage(V₀). It is also connected to conductor 107 through conductor 105 toprovide an input signal of the load output) current (I₀) sensed,processes the input signals to provide an indication of the impedance,power, and voltage and current levels. A readout 123, connected throughconductor 119 to signal measurement and processing circuit 118, provideseach of a plurality of indications of impedance, power, voltage level,current level, etc.

Variable resistors R3 and R4, in combination with operational amplifier120, are representative of adjustments to be made to correlate theoutput current (i_(s)) of the galvanic cell with the tissue temperatureof ablation site 20. Calibration circuit 116 can perform theabove-described correlation of the thermistor indicated temperature withthe current output signal of the galvanic cell to obtain a tissuetemperature indication of the ablation site as a function of the current(i_(s)) generated by the galvanic cell. A readout 122, connected viaconductors 124,126 with the calibration circuit, may be employed toprovide an indication of the tissue temperature of the ablation site. Anoutput signal from the calibration circuit is also conveyed viaconductors 124 and 128 to servo amplifier 94. This output signal isreflective of the tissue temperature at the ablation site. Thereby, theservo amplifier receives an input signal reflective of the tissuetemperature at the ablation site. Circuitry of servo amplifier 94 willdetermine whether to raise or lower the tissue temperature of theablation site or to maintain it at its preset temperature. A commandsignal to increase, to decrease, or to maintain the power output of theRF generator is transmitted from servo amplifier 94 through conductor 96to the RF generator.

Referring to FIG. 6, there is illustrated a variant of probe 14 useablewith the present invention. The combination of first mapping a site ofinterest and then ablating the site is a lengthy procedure. Were itpossible to ablate a site identified during a mapping procedure withoutrelocating the probe or without replacing the mapping probe with anablating probe, significant time would be saved. FIG. 6 illustrates acatheter probe 130, which may be sufficiently flexible to position allor some of its length in contacting relationship with the surface of themyocardial tissue to be mapped. A tip 132, which may be similar to tip30 of probe 14, is disposed at the distal end. A plurality of mappingelectrodes, such as rings 134, 136, 138, 140 and 142 are disposedproximally along the probe from tip 132. These rings serve a function ofmapping the tissue of interest to identify and locate a site to beablated to destroy the circuit responsible for errant impulses. For someor all of these rings to work in the manner of tip 30, as described withreference to FIGS. 1-5, the rings are preferably metallic and have awork function different from that of plate (or electrode) 34.Alternatively, one or more of the rings may serve in the manner of plate34 by being formed of copper or other metal having a work functiondifferent from that of the remaining rings or the tip. Thereby, the needfor plate 34 is eliminated. One of a plurality of conductors 144, 146,148, 150, 152 and 154 interconnect the respective tip and rings with theoutput of a switching circuit(s) 160. A data acquisition circuit 162 isselectively interconnected through switching circuit 160 to each ofrings 132-142 and possibly tip 132. The data acquisition circuitcollects data sensed by the rings and/or tips to map the tissue surfacetraversed by the probe. Upon detection of a site to be ablated todestroy an impulse pathway (circuit), switch circuit 160 switches tointerconnect the respective ring(s) (or tip) with RF generator 164. Uponsuch interconnection, the respective ring(s) (or tip) will irradiate theidentified site with RF energy and the ablation function, as describedabove along with the tissue temperature control function, will beperformed.

From this description, it is evident that upon detection of a sitelocated by performing a mapping function, ablation of the site can beperformed immediately without further movement or manipulation of thecatheter probe. Furthermore, the ablation function can be performed withthe circuitry illustrated in FIG. 5 to heat and maintain the tissue at apredetermined temperature until ablation is completed.

Empirically, it has been determined that the circuit and apparatus forablating tissue, as illustrated in FIG. 5, provides to a physician avery accurate indication of the tissue temperature at the ablation site.With such accuracy, ablation procedures are capable of being performedon thin wall tissue without fear of coagulation of the tip, adhesion oftissue to the tip or puncture, which fears exist with presently usedablation performing apparatus. Furthermore, accurate representation ofthe temperature at the ablation site is no longer critically dependentupon the orientation of the probe at the ablation site nor upon theextent of the depression of the tissue in response to the pressureexerted by the probe tip. Because of these very difficult to controlvariables, complete ablation of the errant impulse pathway was notalways achieved if the physician were overly cautious. Tip coagulation,sticking tissue and sometimes excessive injury to and puncture of thetissue occurred if the physician were more aggressive. These resultswere primarily due to the inaccuracy of the information conveyed to thephysician during the procedure and not so much due to poor technique.

As will become evident from the above description, tip 30 (and tip 132)does not need a thermistor or a thermocouple to set or determine thetemperature of the ablation site. Therefore, the probe can be smallerand more versatile than existing probes. Moreover, the probe can bemanufactured at a substantially reduced cost because it is more simplethan existing devices. Rings (or other electrodes) located on thecatheter can be used for mapping sites of errant impulses and any of therings (or other electrodes) can be used to irradiate the tissue at suchsite after identification of the site and without repositioning of thecatheter.

As a result of in vivo testing on canines in conjunction with moreaccurate and expanded signal displays, a further important capability ofthe present invention has been uncovered. Referring to FIG. 7A, there isillustrated a graph of three signals present during an ablationprocedure. The ordinate of the graph depicts time in seconds and theabscissa depicts voltage. Curve 170 depicts the RF power level appliedto catheter tip 30 and the voltage scale is proportional to the powerlevel. The power applied is shown as steps 172, 174 and 176. The poweris maintained essentially constant at each of these power levels. Thepower is turned on at time T₁ and turned off at time T₂. Curve 180depicts the output of the thermistor within tip 30 (such as thermistor Twithin tip 60 shown in FIG. 3) and the voltage scale is proportional tothe temperature sensed by the thermistor. Prior to time T₁, section 182of curve 180 is essentially quiescent and representative of anessentially constant temperature. Upon application of power, thetemperature recorded by the thermistor increases, as depicted by section184, which increase is essentially correlated with the time of powerlevel 172. Upon further increase of the power level (174) section 186depicts a higher temperature. Similarly, upon application of power level176, section 188 depicts a yet higher temperature level. Aftertermination of the power applied at time T₂, the temperature of thethermistor drops, as depicted by section 189.

The current (I_(o)) generated by the galvanic cell is represented bycurve 190 and the voltage scale is proportional to the current. Prior totime T₁, the current is essentially constant, as depicted by segment192. At time T₁ and upon application of RF power, the current increases,as depicted by segment 194, until a quiescent state is established afteran initial duration of applied power corresponding with power level 172.Upon an increase of applied power level 174, the current increasessharply in segment 196. During the latter time period of power level174, the rate of increase of current during segment 196 decreases. Uponapplication of additional power, represented by power level 176, therate of increase of current level depicted by segment 198 remainsessentially constant to a peak identified by numeral 200. It is to benoted that this peak occurs after power corresponding with power level176 has been applied for a short duration. Thereafter, the currentsteadily decreases (decays). It may be noted that the peak of the curverepresenting the temperature of the thermistor, and depicted by point188A, occurred significantly later than the peaking of curve 190 atpoint 200.

The cause for peaking of the current produced by the galvanic cellduring application of a constant power level was not immediatelyunderstood nor evident from the data. Upon further inspection of an invivo ablation site in the heart of a canine, it was learned that peakingoccurred simultaneously with tissue damage (discoloration) at theinterface between the catheter tip and the tissue. It is believed thatthe tissue damage resulted in a change in ion and cation distribution,or change in charge distribution, at the ablation site. That is, theresulting environment of damaged tissue having a reduced chargedistribution significantly affected the current generated by thegalvanic cell and provided a clear and unambiguous signal.

From these results, one can then draw the following conclusions. First,and as set forth above, the output current of the galvanic cell iscorrelatable as a function of the temperature of an ablation siteirradiated with RF energy. Second, the current output of the galvaniccell formed by the subject undergoing an ablation procedure provides anunambiguous and readily apparent indication (signal) of when the tissuesought to be ablated at an ablation site has in fact been ablated.Third, upon detection of peak 200 during an ablation procedure, furtherapplication of RF power may be terminated. Since ablation generallyrequires a temperature in the range of about 50 to 55 degreesCentigrade, conditions giving rise to tip coagulation, sticking tissueand perforation of the tissue will not occur. The resulting safetyfeature of the ablation procedure and the elimination of seriouspossibility for consequential injury will be achieved to a degree neverbefore available.

Referring to FIG. 7B, there is representatively shown a curve 210depicting applied RF power levels, curve 212 depicting the temperatureof a thermistor disposed in a catheter tip performing an ablationprocedure, and curve 214 depicting the current output of a galvanic cellwhich would be present during an ablation procedure. Curve 214 depicts apeak 216 occurring during application of power corresponding with powerlevel 218. At this power level, segment 220 of curve 212 has an initialrise followed by a reduced rate of rise of temperature. Despite theconstantly applied power level, curve 214 decreases subsequent to peak216. Upon application of a higher power level, represented by numeral220, the decrease of curve 214 is halted and after a small risemaintains an essentially quiescent state. However, segment 224 of curve212 increases abruptly with a following reduced rate of increase. Upontermination of power at T₂ curves 214 and 212 decrease.

The curves depicted in FIG. 7B clearly show that peak 216 occurring incurve 214 is unaffected by subsequent applications of increased powerand despite such increased power provides an unambiguous indication ofablation of the tissue at an ablation site.

It is presently believed that the degree of decay of the current signal(curve 180 or 214) is a function of the tissue damage. Moreover, it isbelieved that the depth of ablation can be controlled as a function ofpower level and time subsequent to occurrence of ablation (peak 200 or216).

Referring to FIG. 8, there is illustrated an improved version of theapparatus shown in FIG. 5. The improved version includes a computer 250which includes a visually perceivable display screen 251 for depictingdata, two-dimensional images, etc. For example, readout 123 (depicted inFIG. 5) may be one of the group of images that would be displayed bycomputer 250. The computer may include a plurality of ports, representedby block 252, through which data, whether digital or analog, may beinputted and outputted. Load/impedance measurement circuit 118 isconnected to a port 254 of block 252 via conductor 256. The computer 250includes the capability for manually or otherwise inputting data thatwould affect the parameters, operation, or results achieved during anablation procedure. A port 258 will provide, through conductor 260, anon/off switching function for RF generator 98. A reference voltagerepresentative of a temperature can be applied to servo amplifier 94through conductor 262 via port 264. The readout function formerlyperformed by readout 122 (see FIG. 5) can be provided by computer 250 byinterconnecting conductor 266 via port 268. Furthermore, the curvesdisplayed in FIGS. 7A and 7B may be readily displayed by computer 250through use of its display screen 251.

With the use of a computer and associated software, it is now possiblefor a surgeon to determine on a real time basis the exact momentablation occurs at an ablation site by denoting the presence of peak 200(FIG. 7A) or peak 216 (FIG. 7B). Thereafter, further application of RFpower is unnecessary and all of the potential hazards of overheating atthe ablation site are avoided. However, as the depth of ablation in thetissue is or may be a function of the power level per time of applied RFpower, radiation of RF energy may be continued until the level ofablation desired by the surgeon is achieved.

As discussed above, a catheter tip having multiple elements, as depictedin FIG. 6, can be used to simultaneously or sequentially ablate each ofa plurality of sites. The use of a computer 250 permits real timemonitoring of each ablation site. With such monitoring, control of RFpower applied to each ablation site is readily available to a physician.

From the experiments conducted that produced curves 190, 210 shown inFIGS. 7A and 7B it became evident that at the peak value of thesecurves, ablation occurred and a lesion was formed. This discovery wassignificant since heretofore such unambiguous signal had not beenavailable to a physician performing the procedure. However, theexperiments did not provide clear and unequivocal information relatingto the size and depth of the lesion formed. To explore further theextent of information contained in or provided by the current outputsignal of the galvanic cell, further experiments were conducted.Moreover, the galvanic cell began to be referred to by the trademarkBio-Battery owned by the present assignee and such nomenclature will beused herein form time to time.

As set forth above, the underlying mechanism of the Bio-Batterytechnique is that when electrodes of two dissimilar metals are placed incontact with tissue, a galvanic current is generated. When this currentpasses through load resistance, a output current signal can be measuredthat relates to the combination of the intrinsic property of theelectrode metal and temperature, as well as local ionic concentrationand the ratio of the oxidized and reduced forms of these ions. Duringthe course of RF energy application, the output current signal exhibitsa characteristic change that may reflect the local change of myocardialtissue properties. These characteristic changes of the output currentsignal may indicate the process of myocardial lesion formation. A seriesof experiments were developed to explore the characteristics of theoutput current signal and determine if it can be used to predictmyocardial lesion formation and to determine lesion depth. As a result,in vitro and in vivo experiments were performed, which will be describedin detail below.

As shown in FIG. 9, all in vitro experiments were performed with a7-French EPT catheter 250, (EP Technologies 6303 and 6304, Sunnyvale,Calif.). This catheter configuration has a thermally isolated thermistormounted on the tip 252 of a 4 mm distal electrode. RF power wasdelivered with a computer-controlled custom RF generator 254 made by thepresent assignee and described previously, which has the capacity todisplay on-line and record biophysical parameters of RF power output,thermistor-tissue interface temperature, bio-battery cell current(output current signal of galvanic cell) and tissue impedancesimultaneously. Fresh bovine ventricular myocardium 256 was immersed ina temperature-controlled bath with circulating fresh bovine blood 258 at37° C. at a flow rate of 2 liter/minute within a bowl 260. A copperreturn plate 262 was placed under the myocardium. Distal tip electrode252 was oriented perpendicular to the cut surface (and upon theepicardial or endocardial surfaces in certain experiments) of themyocardium and held in place by a stand 264. The electrode-tissuecontact was assessed by a pre-ablation tissue impedance. Each procedurewas repeated six times at different sites, unless otherwise mentioned.On-line data of RF power output, thermistor-tissue interfacetemperature, the bio-battery cell output (output current signal ofgalvanic cell) and tissue impedance was displayed simultaneously andrecorded for off-line analysis, as shown in FIG. 10. Lesions formed atall of the ablation sites were first measured grossly, and again afterstaining with nitro blue tetrazolium (NBT). Lesion dimensions arepresented as length×width×depth. Lesion volume is presented as 2/3πr1×r2×d (xxx). All data are presented in the format of Mean±Standarddeviation. One way ANOVA analysis and post-hoc testing as well as aStudent t-test were performed. A p value smaller that 0.05 is consideredas statistically significant.

To correlate lesion depth with varying termination criteria, RF energy,electrode-tissue temperature and duration of RF application, thefollowing protocol was performed. Tip 252 was placed on the cut surfaceof myocardium 256 at a contact pressure of approximately 12 grams, asshown in FIG. 9. The following tests were conducted and FIGS. 10 and 11are generally representative of the signals observed:

1) RF energy was applied at a constant level of 20 volts until arespective 20, 40 and 60 percent drop in bio-battery output currentsignal 270 relative to the maximum value of the output current signaloccurred.

2) RF energy was applied at a constant level of 30 volts until arespective 20, 40 and 60 percent drop in bio-battery output currentsignal 270 occurred and a rapid and marked impedance rise 272a occurred(impedance rise is defined as an impedance greater than 200 ohms).

3) RF energy was applied at a constant level of 40 volts until arespective 20, 40 and 60 percent drop of the maximum bio-battery outputcurrent signal 270 occurred and until there was a rapid and marked risein impedance 272a.

4) RF energy was applied at a constant level of 50 volts until arespective 20, 40, and 60 percent drop in bio-battery output currentsignal 270 occurred and until there was a rapid, marked rise inimpedance 272a.

5) RF energy was applied at a constant 50 volt level until a first"Bump" 274 occurred (the "Bump" is characterized by the momentaryincrease (inflection) in the bio-battery output current signal after thedecrease following a maximum value of the output current signal).

To obtain data regarding the bio-battery signal in different types oftissue, the 50 v and 12 gram protocol was repeated on epicardial andendocardial surfaces of the myocardium.

In vitro test results are summarized in Table 1 below.

                                      TABLE 1                                     __________________________________________________________________________    TURN OFF OF RF ENERGY UPON BIO-BATTERY OUTPUT                                 CURRENT SIGNAL DECREASE AT OCCURRENCE OF IMPEDANCE RISE OR                    OCCURRENCE OF BUMP                                                            Initial Gross                                                                              Stained          RF   Temp. Cell                                 Imped.  depth                                                                              depth                                                                              Volume                                                                             RF     Power                                                                              Max   Temp Maz                             (ohms)  (mm) (mm) (mm.sup.2)                                                                         duration                                                                             (watts)                                                                            (° C.)                                                                       (° C.)                        __________________________________________________________________________    20 volt                                                                       20$     1.7 ± .1                                                                          --  90 ± 18                                                                        168.3 ± 32.7                                                                       2.3 ± .4                                                                       51.4 ± 3.7                                                                       54.5 ± 6.8                        40%     3.0 ± 2                                                                           --   -- 179.8 ± .1                                                                         2.1 ± .2                                                                       48.6 ± 4.5                                                                       52.9 ± 8.2                        60%       --   --   --   --     --   --    --                                 Imped.    --   --   --   --     --   --    --                                 Rise                                                                          30 volt                                                                       20%     2.4 ± 2.0                                                                            146 ± 124                                                                       103.9 ± 83.7                                                                       5.1 ± .2                                                                       58.7 ± 8.4                                                                       63.4 ± 10.6                       40%     3.9 ± .2                                                                             234 ± 48                                                                        105.3 ± 64.8                                                                       5.4 ± .1                                                                       61.2 ± 5.7                                                                       69.7 ± 5.5                        60%       5 ± .4                                                                        4.7 ± .6                                                                        377 ± 118                                                                       133.6 ± 54.2                                                                       5.4 ± .1                                                                       61.2 ± 4.7                                                                       69.7 ± 5.5                        Imped.  5.7 ± 1.2                                                                       6.1 ± 1.6                                                                       567 ± 341                                                                       179.7 ± 0                                                                          5.5 ± .1                                                                       61.5 ± 2.4                                                                       81.7 ± 7.5                        Rise                                                                          40 volt                                                                       20%     3.8 ± .8                                                                        4.0 ± .9                                                                        242 ± 67                                                                         35.5 ± 25.7                                                                       8.2 ± .2                                                                       69.5 ± 4.4                                                                       76.3 ± 3.8                        40%     4.4 ± 1.1                                                                       4.8 ± 1.1                                                                       298 ± 109                                                                        44.4 ± 29.1                                                                       8.3 ± .4                                                                       70.8 ± 3.1                                                                       79.6 ± 3.3                        60%     4.0 ± .9                                                                        4.5 ± .8                                                                        320 ± 124                                                                        17.7 ± 10.5                                                                       8.2 ± .3                                                                       73.7 ± 6.5                                                                       83.4 ± 3.1                        Imped.  8.1 ± 1.4                                                                       8.1 ± 1.4                                                                       751 ± 313                                                                       140.9 ± 50.8                                                                       7.5 ± .4                                                                         68 ± 2.4                                                                       88.5 ± 7.1                        Rise                                                                          50 volt                                                                       20%     3.8 ± .7                                                                        4.3 ± .5                                                                        208 ± 55                                                                         22.5 ± 7.3                                                                       13.1 ± .3                                                                       71.6 ± 2.7                                                                       78.3 ± 1.9                        40%     3.9 ± .6                                                                        4.9 ± .9                                                                        298 ± 41                                                                         14.3 ± 3.8                                                                       12.8 ± .1                                                                       75.4 ± 2                                                                         83.3 ± 1.8                        60%     4.4 ± .7                                                                        4.6 ± .6                                                                        359 ± 55                                                                         18.8 ± 12.8                                                                      12.6 ± .2                                                                         73 ± 2.3                                                                         84 ± 2                          Bump    6.8 ± 1                                                                         6.3 ± 1.2                                                                       758 ± 360                                                                        71.6 ± 40.5                                                                      12.8 ± .2                                                                       76.3 ± 2                                                                         90.2 ± 1.5                        Imped.  8.2 ± .9                                                                        8.6 ± 1.2                                                                       906 ± 366                                                                         52 ± 33.9                                                                       12.2 ± .3                                                                       76.3 ± 2                                                                         92.5 ± 1.4                        Rise                                                                          __________________________________________________________________________

As shown in FIG. 10, at the onset of RF energy delivery, bothbio-battery output current signal 270 and electrode-tissue interfacetemperature 276 rapidly rose. At the same time, tissue impedance 272first decreased, then flattened. It has been consistently observed thatat a temperature above 70±° C., the bio-battery output current signal270 reaches a maximum level followed by a decrease well before the steeprise 272a in impedance 272 is observed. At the time of the decrease 270a(turndown) of the bio-battery output current signal RF lesions wereconsistently formed. A few seconds immediately before the tissueimpedance 272a rises, there is a "Bump" 274 in the bio-battery outputcurrent signal 270. In some cases, there was more than one "Bump" in thebio-battery output current signal. The mean temperature 276 at the"Bump" is 85±° C. and the mean temperature at the point of impedancerise is 90±° C. In most cases, if RF energy was continuously appliedafter this "Bump" signal, a series of audible "pops" would sound andrapid impedance rise would follow (These "pops" are believed to be thesounds of cells simultaneously exploding, which explosion woul injectdebris (clots) into the blood and could cause a stroke). Between thepoint of maximum bio-battery output current signal and the "Bump" andbetween the "Bump" to rapid impedance rise, there are "window times" of30±seconds; and 5±seconds, respectively; note also FIG. 11. Since this"Bump" precedes the occurrence of rapid impedance rise, it could be usedas a termination signal to avoid impedance rise or/and "POP". During theexperiment, one protocol was added that terminated the RF energyapplication at Bump 274 of bio-battery output current signal 270.

As shown in Table 1, as the RF energy level increases, a higheramplitude of bio-battery output current signal was observed. At RFlevels of 40V and 50V, myocardial lesions were consistently formed. Forexample, in the 50V group, when RF energy application was terminated atthe points of 20, 40 60% of the peak for the bio-battery output currentsignal, average lesion depth was 3.6-4.4 mm. However, when RF energyapplication was terminated at the Bump point (274), 6.8±1 mm deeplesions were created. The average lesion depth of the Bump point groupof lesions was not significantly different than the depths of theimpedance rise group of lesions, which had an 8.6±0.9n mm average depth,as shown in FIG. 12. These data suggest that depth of lesions created atthe Bump point of the bio-battery output current signal are almosttwofold deeper than those created at the points of RF terminationcorresponding with the 20, 40 and 60% output current signal points butare not significantly different than those created at the point of rapidimpedance rise. The protocol of lesion formation with RF energyapplication terminated at the Bump point was repeated on the epicardialand endocardial surfaces of the myocardium. The depth of these lesionsmade in the epicardial and endocardial surfaces were not statisticallydifferent than those made on the cut surface.

For in vivo experiments, a mongrel dog was used. The dog wasanesthetized using isoflurane and mechanically ventilated. A copperreturn plate was placed in direct contact with the skin on the dorsalsurface after shaving the hair. Conductive gel was used between theanimal skin and the return plate (similar to plate 34 shown in FIGS. 1,2, 5 and 8 and plate 262 shown in FIG. 9).

A 7-French EPT catheter (EPT 6304) and a 7-French Webster catheter(Cordis Webster, Calif.) with a thermocouple mounted in the center ofthe distal electrode were used. The RF generator and on-linecomputerized control system described in the in vitro experiments wereused. RF energy was delivered in monopolar mode and a copper back platewas used as the RF return electrode. The experimental procedure isdescribed as follows.

The EPT catheter was inserted into the left ventricle (LV) through theright femoral artery. RF energy was applied to different sites of theleft ventricle with the distal electrode positioned perpendicular to theendocardium as assessed by fluoroscopy. The electrode-tissue contact wasconfirmed by observing an increase in tissue impedance and current ofinjury in the unipolar intra-cardiogram. All six positions werepredicted as having good electrode--tissue contact. RF energy wasdelivered at six positions in the left ventricle. Constant RF voltage of50±1 volts was applied until the bio-battery output current signaldropped 20% from its peak, at which time RF energy application wasautomatically terminated. The results are tabulated in Table 2 below:

                                      TABLE 2                                     __________________________________________________________________________    LV                                                                                    Pre Z                                                                            Post Z                                                                            Duration                                                                           RF Power                                                                             Final T                                            Test                                                                             Loch Ω                                                                          Ω                                                                           (sec)                                                                              volts                                                                            (watts)                                                                           (° C.)                                                                     Lesion (mm)                                    __________________________________________________________________________    1  LV apex                                                                            220                                                                              195 50   49 9   80  8 × 5 × 4 endo.                                                   subs: 9 mm L                                   2  LV mid                                                                             205                                                                              180 180  48 13.3                                                                              80  7 × 5 × 7 endo.                       anterior                    Subs: 8 mm L                                   3  LV high                                                                            205                                                                              175 110  48 11.2                                                                              88  5 × 5 × 4                                                         subs: 5 × 8 mm                           4  LV   200                                                                              170 30   51 18  88  10 × 5 endo.                                                            (subs) 10 mm L                                 5  LV   205                                                                              170 45   51 12.7                                                                              84  5 × 5 × 5 endo.                       anterior                    subs: 7 mm W                                   6  LV   180                                                                              175 40   51 14.5                                                                              90  5 × 5 × 8 endo.                       lateral                                                                    __________________________________________________________________________

Using the same criteria as above, the Webster catheter was placed intothe right ventricle (RV) under fluoroscopic guidance through the rightfemoral vein. The distal electrode was placed parallel to the myocardiumand RF energy was delivered through this electrode. Four positions in RVwere predicted as having good electrode--tissue contact. On the last RVposition, good tissue contact was obtained then the catheter waswithdrawn to maintain minimum contact. RF energy was delivered at fivepositions in the right ventricle. Constant RF energy output of 57±4volts was applied until the bio-battery output current signal dropped20% from its peak, and RF energy application was then automaticallyterminated. The results are tabulated in Table 3 below:

                                      TABLE 3                                     __________________________________________________________________________            Pre Z                                                                            Post Z                                                                            Time  Power                                                                             Final T                                                                           Lesion                                           Test                                                                             Loch Ω                                                                          Ω                                                                           (sec)                                                                            Volts                                                                            (watts)                                                                           (° C.)                                                                     L × W × D                            __________________________________________________________________________    1  RV OT                                                                              225                                                                              165 20 51 11.6                                                                              100 8 × 5 × 4                                                         subs: 9 mm L                                     2  RV apex                                                                            205                                                                              160 25 55 14.8                                                                              94  5 × 5 × 3.5                                                       Subs: 8 mm L                                     3  RV OT                                                                              200                                                                              160 55 53 14.1                                                                              99  6 × 6 × 4                               high                      subs: 7 mm L                                     4  RV apex                                                                            180                                                                              170 220                                                                              57 18.1                                                                              56  can't locate                                     5  RV near                                                                            170                                                                              180 205                                                                              60 21.2                                                                              60  2.5 × 2.5 mm                                  apex                      endo                                                                          5 mm diam epi.                                   6  RV under                                                                           205                                                                              170 85 53 13.7                                                                              77  5 × 10,                                       TCV                       superficial                                      __________________________________________________________________________

The same Webster catheter mentioned above was placed in the right atrium(RA) under fluoroscopic guidance through the right femoral vein. Theelectrode-tissue contact was predicted by the rise in tissue impedanceand current of injury observed in the unipolar intracardiogram. RFenergy was delivered until the bio-battery output current signal dropped20% from its peak at which time RF energy application was automaticallyterminated. The results are tabulated in Table 4 below:

                                      TABLE 4                                     __________________________________________________________________________                                 Lesion                                                   Pre Z                                                                            Post Z                                                                            Time                                                                             RF Power                                                                             Final T                                                                           L × W × D                            Test                                                                             Loch Ω                                                                          Ω                                                                           (sec)                                                                            (V)                                                                              (watts)                                                                           (° C.)                                                                     (mm)  notes                                      __________________________________________________________________________    1  RA high                                                                            195                                                                              190 240                                                                              47 11.3                                                                              67  can't                                                                         locate                                           2  RA   240                                                                              200 165                                                                              50 10.4                                                                              73  5 × 5                                         append.                                                                    3  RA   205                                                                              180 n/rec                                                                            53 13.7                                                                              72  7 × 7                                                                         transmural                                    lateral     d                                                                 wall                                                                       4  RA mid                                                                             235                                                                              200  5 70 20.9                                                                              88  7 × 7                                                                         transmural                                    septal                                                                     __________________________________________________________________________

In all these procedures, RF power output, electrode-tissue interfacetemperature, bio-battery output current signal and tissue impedance wasdisplayed simultaneously and stored for future analysis. FIG. 13 isrepresentative of these signals. Gross examination of the heart wasperformed after sacrificing the animal and the lesion sizes weremeasured and recorded.

The results of the in vivo study are summarized in Tables 2, 3 and 4above. In the left ventricle, RF energy delivery ranged from 9 to 15watts and duration ranged from 30 to 180 seconds. Maximum bio-batteryoutput current signals and signal inflections (bump 274) were observedin all six RF applications. Six white, homogeneous endocardial lesionswere observed and measured during the pathological examination of theheart (Table 2). In the right ventricle, four solid lesions wereobserved and measured. corresponded to those positions which werepredicted to have good tissue contact and which had a cell signalturndown (Table 3). In the right atrium three out of the four atriallesions were transmural (Table 4).

Temperature monitoring has been proposed as a control mechanism forlesion formation and dimension during radio-frequency trans-catheterablation. Effective measurement depends on thermocouple or thermistorposition relative to the heated cardiac tissue and the conductivecooling effects of the circulation. The accuracy of a single tipthermistor as a measure of peak electrode-tissue interface temperatureis unknown. Also the accuracy of a single tip thermistor is dependent oncatheter-tissue orientation. Catheters that utilize thermistors andthermocouples for temperature monitoring are currently available,however, measured electrode-tissue interface temperature is not accuratedue to the varying orientation of the tip and the cooling effect of thesurrounding blood flow. Additionally, mounting thermocouples orthermistors on a multiple electrode catheter is technically difficultand expensive.

To achieve safe operation and optimal lesion formation, otherbiophysical parameters such as tissue impedance, power consumption, andon-line unipolar electrograms monitoring have been also explored toregulate RF energy application as well as to predict lesion formationand depth for RF ablation. However, these parameters appear to have alack of adequate sensitivity and consistency to reflect the real tissuetemperature and on-going changes of tissue properties.

The bio-battery output current signal and the thermistor-measuredelectrode tissue interface temperature correlate well between the rangeof 35° C.-70° C. These results indicate that RF ablation temperature maybe monitored with catheters without embedded thermocouples orthermistors. Evidence obtained from these studies suggest that decreasedbio-battery output current signal during lesion formation reflected theprogression of lesion formation. Therefore, the bio-battery outputcurrent signal indicates feedback control signal to control RFapplication in order to avoid blood coagulation on the catheterelectrode and tissue charring, as indicated by rapid impedance rise, asdepicted in FIG. 10. More significantly, the bio-battery output currentsignal might be useful to determine the lesion depth and size during theRF application and it may help cardiologists to create lesions withdesirable depth and size. For example, one might want to create lesionin the atrium with less depth than in the ventricles, since the atrialwall is much thinner than the ventricle wall. The termination of RFenergy application at the peak of the bio-battery output current signalmight be sufficient to achieve that goal. On the other hand, to treatventricular tachycardia, it might be desirable to terminate RFapplication at Bump 274 of the output current signal 270 in order tocreate the deepest possible lesion without rapid impedance rise and a"POP". Another feature of the bio-battery output current signal is thatamplitude and morphology of the signal is sufficiently different betweenablated and un-ablated tissues. This feature might be useful forcardiologists to distinguish these two tissue conditions during thecourse of mapping and ablation and therefore reduce operation time andunnecessary damage to myocardial tissue.

Data from this study suggests that with the use of the bio-batterytechnique, predicting myocardial lesion formation and determining lesiondepth and size is possible during RF energy application, using aconventional catheter. The bio-battery technique may provide a usefulmarker to predict lesion formation without using a thermistor or athermocouple, thereby aiding in more stable and maneuverable catheters.Maximum bio-battery output current signal not only predicts lesionformation, but also may be used to provide a feedback to regulate powerapplication to prevent coagulum formation and rapid impedance rise. Thistechnique may be particularly beneficial when making long linear lesionswith a multiple electrode catheter.

Recently, the application of saline irrigation catheters has gained muchinterest, because of its ability to apply increased RF energy withoutthe risk of blood-coagulation on the electrode and rapid impedance rise.However, since there is no accurate tissue temperature monitoring duringan RF energy application in vivo, the technique is virtually "blind" interms of tissue temperature. As a consequence, "Bubble and POP"formation in deep tissue, and therefore perforation and severe workingmyofiber damage may occur if excessive RF energy was delivered. Sincethe bio-battery output current signal may reflect the change of localtissue property, and as it provides a marker for "Bubble and Pop"formation, it could be useful as a safety measure to assist in theapplication of saline irrigation catheter.

In summary, our preliminary data demonstrated that the bio-batterytechnique provides unique biophysical parameters that might be usefulfor safe and optimal RF ablation for the treatment of cardiacarrhythmias. It is clear the bio-battery technique possesses advantagesover other biophysical parameters to provide control signal and safetymarkers for RF ablation.

While the invention has been described with reference to severalparticular embodiments thereof, those skilled in the art will be able tomake the various modifications to the described embodiments of theinvention without departing from the true spirit and scope of theinvention. It is intended that all combinations of elements and stepswhich perform substantially the same function in substantially the sameway to achieve the same result are within the scope of the invention.

What is claimed is:
 1. Apparatus for ablating tissue at an ablation sitein the heart of a human being while avoiding the possibility of tipcoagulation, tissue sticking or tissue perforation, said apparatuscomprising in combination:(a) a source of RF energy for irradiating thetissue at the ablation site to cause a temperature rise of the tissue atthe ablation site; (b) a catheter having a first electrode forcontactingly engaging the ablation site and for irradiating the tissuewith RF energy to heat the tissue at the ablation site, said electrodecomprising a first electrode of material having a first work function;(c) transmission means for conveying RF energy from said source to saidfirst electrode; (d) a second electrode displaced from said firstelectrode and of material having a second work function different fromthe first work function for electrically contacting an area of tissue ofthe human being; (e) a galvanic cell formed by said first electrode,said second electrode and the tissue of the human being serving as anelectrically interconnecting electrolyte for generating an electricalsignal having a peak value corresponding with initial occurrence ofablation of the tissue at the ablation site followed by a decreasingvalue, an inflection in value and a decreasing value; and (f) a controlcircuit responsive to said electrical signal generated by said galvaniccell for regulating the operation of said source of RF energy to controlRF radiation of the ablation site before and after said electricalsignal has reached a peak value and to terminate radiation of theablation site upon detection of the inflection in value of saidelectrical signal.
 2. A catheter assembly for irradiating tissue at anablation site of a living being to raise the temperature of the ablationsite, to sense the occurrence of a lesion at the ablation site as aresult of ablation, and to terminate heating of the ablation site, saidcatheter assembly comprising in combination:(a) a catheter having afirst electrode locatable at the ablation site, said first electrodebeing formed of a material having a first work function; (b) a secondelectrode displaced from said first electrode and adapted to be inelectrical contact with the tissue of the living being, said secondelectrode being formed of a material having a second work functiondifferent from the first work function; (c) a galvanic cell formed bysaid first electrode, said second electrode, and the tissue of theliving being serving as an electrolyte intermediate said first electrodeand said second electrode for generating an output current signalcorresponding to the depth of the lesion in the tissue at the ablationsite and having a characteristic inflection in value representative ofthe occurrence of adequate ablation of the tissue at the ablation site;(d) an RF generator interconnected with said first electrode and saidsecond electrode for applying RF energy through said first electrode tothe tissue at the ablation site to heat the tissue at the ablation site;and (e) a control circuit for regulating said RF generator as a functionof the characteristic of said output current signal.
 3. Apparatus forablating tissue at an ablation site, said apparatus comprising incombination:(a) an RF generator for applying RF energy to the ablationsite to heat the ablation site tissue; (b) a probe having a firstelectrode adapted to be in contact with the ablation site tissue forirradiating the ablation site tissue with RF energy; (c) a transmissionline for conveying RF energy from said RF generator to said probe; (d) agalvanic cell for sensing ablation at the ablation site tissue and forproducing an output current signal having an inflection in value after adecrease in value reflective of the ablation sensed, said galvanic cellincluding: said first electrode adapted to be located at the ablationsite, a second electrode adapted to be displaced from the ablation site,and an electrolyte in electrical contact with said first and secondelectrodes; and (e) a control circuit responsive to the inflection invalue of said output current signal produced by said galvanic cell forcontrolling the RF energy applied to said probe.
 4. A method forablating tissue at an ablation site in the heart of a human being, saidmethod comprising the steps of:(a) generating RF energy from a source ofRF energy; (b) conveying RF energy from the source to a first electrodein contact with the ablation site; (c) irradiating the tissue at theablation site with RF energy from the first electrode to heat the tissueat the ablation site, the first electrode being comprised of materialhaving a first work function; (d) electrically contacting an area oftissue of the human being with a second electrode displaced from thefirst electrode and of material having a second work function differentfrom the first work function; (e) generating an output current signalreflective of the occurrence of ablation of the tissue at the ablationsite with a galvanic cell formed by the first electrode, the secondelectrode and the tissue of the human being serving as an electricallyinterconnecting electrolyte; and (f) regulating the operation of thesource of RF energy with a control circuit responsive to an inflectionin value of the output current signal generated by said generating stepto control RF irradiation of the ablation site.
 5. A method for ablatingtissue at an ablation site, said method comprising the steps of:(a)generating RF energy with an RF generator; (b) conveying RF energy fromthe RF generator through a transmission line to a first electrode of aprobe; (c) irradiating the ablation site with RF energy through thefirst electrode proximate the ablation site; (d) producing a signalreflective of the occurrence of ablation at the ablation site tissuewith a galvanic cell, the galvanic cell comprising the first electrode,a second electrode displaced from the first electrode and an electrolytein electrical contact with the first and second electrodes; and (e)regulating the output of the RF generator with a control circuitresponsive to an inflection of the signal produced by said producingstep.
 6. Apparatus for detecting the occurrence of ablation of tissue atan ablation site, said apparatus comprising in combination:(a) acatheter having a tip for contacting the ablation site to irradiate theablation site with RF energy to heat the tissue; (b) a source of RFenergy for transmitting RF energy to said tip; (c) a galvanic cell usingthe tissue as an electrolyte for generating an electrical signalrepresentative of the occurrence of ablation at the ablation site; and(d) a control circuit responsive to an inflection in value of theelectrical signal for terminating the RF energy transmitted to said tip.7. The apparatus as set forth in claim 6 wherein the electrical signalgenerated by said galvanic cell depicts a peak value upon occurrence ofablation followed by a decrease in value and the inflection in value. 8.Apparatus for sensing ablation of tissue at an ablation site during atissue ablation procedure, said apparatus comprising in combination:(a)a catheter having a tip for irradiating the ablation site with RF energyto perform the ablation procedure; (b) a source of RF energy fortransmitting RF energy to said tip; (c) an electrode adapted to beadjacent tissue; (d) a galvanic cell formed by said tip, said electrodeand the tissue for generating a unique electrical signal having aninflection in value responsive to ablation of the tissue at the ablationsite; and (e) a control circuit responsive to the unique electricalsignal for controlling the RF energy transmitted to said tip.
 9. Amethod for sensing ablation of tissue at an ablation site during atissue ablation procedure, said method comprising the steps of:(a)transmitting RF energy to a tip from a source of RF energy; (b)irradiating the ablation site with RF energy from the tip to perform theablation procedure; (c) locating an electrode adjacent tissue; (d)generating an electrical signal having an inflection in value responsiveto ablation of the tissue at the ablation site with a galvanic cellformed by the tip, the electrode and the tissue; and (e) controlling theRF energy transmitted to the tip with a control circuit responsive tothe electrical signal and terminating said step of irradiating upongeneration of an inflection in value of the electrical signal. 10.Apparatus for sensing ablation of tissue at an ablation site during atissue ablation procedure, said apparatus comprising in combination:(a)a catheter having a tip for irradiating the ablation site with RF energyto perform the ablation procedure; (b) a source of RF energy fortransmitting RF energy to said tip; (c) an electrode adapted to beadjacent the tissue; (d) a generator for generating an electrical signalhaving an inflection in value responsive to ablation of the tissue atthe ablation site, said generator comprising said tip, said electrodeand the tissue; and (e) a control circuit for controlling the RF energytransmitted to said tip as a function of ablation of the tissue and inresponse to the electrical signal.
 11. A method for sensing theoccurrence of ablation of tissue at an ablation site during a tissueablation procedure, said method comprising the steps of:(a) transmittingRF energy from a source of RF energy to a tip; (b) irradiating theablation site with RF energy from the tip to perform the ablationprocedure; (c) locating an electrode adjacent the tissue; (d) generatingan electrical signal having an inflection in value responsive toablation of the tissue at the ablation site with a generator formed bythe tip, the electrode and the tissue; and (e) controlling the RF energytransmitted to the tip with a control circuit as a function of theablation of the tissue and responsive to the electrical signal.